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For the first time, scientists have decoded the molecular structure of a protein that helps to sync a biological clock to the phases of the moon.
The marine bristleworm Platynereis dumerilii syncs its reproductive cycle with the phases of the moon. Scientists recently uncovered the structure of a protein that helps it sense moonlight.
Arne Nygren/Institutionen för marina vetenskaper Göteborgs Universitet
Introduction
On a summer night in the Bay of Naples, hordes of worms swam upward from the seagrass toward the water’s surface under the light of a waning moon. Not long before, the creatures began a gruesome sexual metamorphosis: Their digestive systems withered, and their swimming muscles grew, while their bodies filled with eggs or sperm. The finger-length creatures, now little more than muscular bags of sex cells, fluttered to the surface in unison and, over a few hours, circled each other in a frantic nuptial dance. They released countless eggs and sperm into the bay — and then the moonlit waltz ended in the worms’ deaths.
The marine bristle worm Platynereis dumerilii gets only one chance to mate, so its final dance had better not be a solo. To ensure that many worms congregate at the same time, the species synchronizes its reproductive timing with the cycles of the moon.
How can an undersea worm tell when the moon is at its brightest? Evolution’s answer is a precise celestial clock wound by a molecule that can sense moonbeams and sync the worms’ reproductive lives to lunar phases.
No one had ever seen how one of these moonlight molecules worked. Recently, however, in a study published in Nature Communications, researchers in Germany determined the different structures that one such protein in bristle worms takes in darkness and in sunlight. They also uncovered biochemical details that help explain how the protein distinguishes between brighter sunbeams and softer moonglow.
It’s the first time that scientists have determined the molecular structure of any protein responsible for syncing a biological clock to the phases of the moon. “I’m not aware of another system that has been looked at with this degree of sophistication,” said the biochemist Brian Crane of Cornell University, who was not involved in the new study.
Such discoveries could be relevant to the physiology of many kinds of creatures, including humans. “We have no other example where we understand these mechanisms in such molecular detail,” said Eva Wolf, a biochemist at the Johannes Gutenberg University of Mainz in Germany who is one of the co-authors of the paper. “These studies help us start to know how moonlight oscillators and synchronization with the moon phases can work.”
Though we wake more often today to the blare of an alarm clock than to the first light of dawn, our bodies still keep time with the sun. In humans, as in many other animals, sophisticated biological timepieces called circadian clocks sync the body’s rhythms to the beats of daybreak and nightfall. Cryptochrome proteins are important pieces of many organisms’ circadian clocks, either sensing light, as in plants, or coordinating with other proteins that do, as in humans.
Those aren’t legs on the marine bristle worm Platynereis dumerilii — they’re chitinous bristles used for swimming. The species is a model organism for studying embryogenesis, metamorphosis, regeneration, chronobiology and more.
Mael Grosse
Introduction
Though hundreds of thousands of times fainter than the sun, the moon also illuminates the Earth on a regular schedule. A full cycle, from new moon to full moon and back again, lasts 29.5 days. Many organisms, especially various kinds of marine life, use this lunar calendar as a reliable clock. Corals, mussels, marine worms and even some fish are known to time their reproductive activity to match up with moon phases.
To sync up their circalunar clocks, organisms must somehow sense moonlight and distinguish it from sunlight, which is essentially the same type of light, only far more intense. Exactly how cells manage to keep a lunar calendar — to discern not only moonlight from sunlight, but also a full moon from a new moon — is still largely mysterious.
Recently, scientists have started to wonder if cryptochromes might be involved in lunar clocks, as they are in circadian rhythms. In 2007, scientists found hints in certain corals, which expressed cryptochrome proteins more actively under light.
A few years ago, Wolf joined up with the chronobiologist Kristin Tessmar-Raible of the University of Vienna’s Max Perutz Labs to grow P. dumerilii, since it syncs its reproduction to moon phases. They proved that a light-sensing cryptochrome called L-Cry is a critical piece of the worm’s lunar clock. Their team’s work, published in 2022, showed that the protein can distinguish darkness from sunlight, as well as moonlight.
However, it wasn’t clear how the protein worked. In fact, not a single organism’s circalunar clock was understood at the biochemical level.
“It has been quite overlooked,” Wolf said. “That minor moonlight signal has not been taken seriously. It was always the sun versus darkness.”
To learn how L-Cry works, the researchers wanted to capture how its structure changed when it was exposed to light. Wolf shipped worm L-Cry proteins to the University of Cologne so they could be imaged in Elmar Behrmann’s structural biochemistry lab, which specializes in sensitive, ephemeral proteins. But Behrmann’s experienced team struggled for years to get L-Cry to behave well enough to be imaged by their cryo-electron microscope.
Elmar Behrmann’s lab at the University of Cologne specializes in imaging sensitive proteins. He first purified samples of L-Cry protein with high-performance liquid chromatography (left), then used a cryogenic electron microscope (right) to determine its structure.
Martin Niekämper
Introduction
They didn’t know it at the time, but light was sneaking into the samples. “Probably for one and a half years, when we thought we were working in the dark, we weren’t dark enough,” Behrmann said. After covering every doorway crack and blinking LED with black silicon tape, they finally got a clear picture.
In the dark, P. dumerilii’s L-Cry proteins buddy up as bound pairs called dimers. When they’re hit by intense sunlight, the dimers break apart into two monomers again.
This is the opposite of how light-sensing cryptochromes tell sunlight from darkness in plants, Crane said. Plant cryptochromes group up in sunlight and break apart in the dark.
L-Cry’s moonlight form wasn’t directly captured in these experiments, but the new understanding of the dimer structures reveals how L-Cry distinguishes moonlight from sunlight. The moonlight form of the protein can be created only from the darkness dimer — not from the free-floating sunlight form. This helps explain how worms avoid mistaking the dim light of dawn and dusk for moonlight.
Although this study focuses on just one protein in one animal, there’s reason to think that this lunar timing mechanism is part of an evolutionary story that goes beyond the tragic moonlit romances of the bristle worm. “It’s quite possible that other types of cryptochromes also employ this type of mechanism,” Crane said.
Other animals have monthly reproductive cycles, though they are not necessarily linked to the moon directly. We humans, for example, have a cycle that’s around the same length as the lunar cycle, Tessmar-Raible said. “The menstrual cycle, per definition, is a monthly oscillator.”
Any possible role for moon phases in synchronizing the human menstrual cycle is highly controversial. Even so, menses, months and the moon could share more than etymological roots. The bristle worm hormones that swing in sync with lunar phases have close cousins in humans, Tessmar-Raible said. “I don’t think it’s too far-fetched to say that worms may pave the way for [understanding] monthly reproductive timing in humans.” Perhaps our modern 28-day rhythms are evolutionary leftovers, cobbled together from bits of older cellular clockwork that, in some shallow primordial sea, once helped marine worms keep time to the cycle of the moon.
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